(1) Field of the Invention
The present invention relates generally to surface plasmon resonance. Specifically, the present invention relates to a simple and reliable surface plasmon resonance biosensor device.
(2) Description of the Related Art
Life phenomena are results of biomolecular interactions. Biomolecular interactions are traditionally studied using techniques such as enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), and affinity chromatography. Surface plasmon resonance (SPR) biosensing technique provides two main advantages over these techniques. First, the biomolecular interactions can be monitored in real-time. Second, it is not necessary to label the interacting biomolecules. Surface plasmon is a quantum name for an electric charge density wave that propagates on an interface between a metal and a dielectric, just like photon is a quantum name for a light wave. Surface plasmons are described in U.S. Pat. No. 7,084,980 to Jones, et al. hereby incorporated herein by reference in its entirety. Surface plasmons resonate upon excitation by electromagnetic radiation entering an interface of metallic material and a dielectric material. The surface plasmon responds to changes in the environment in close proximity to the interface. This fact makes surface plasmon resonance useful for the detection of biomolecular interactions. A practical and commonly used method by which to excite the surface plasmon was initially suggested by Kretschmann (Kretschmann, E. (1971) “Die Bestimmung optischer Konstanten von Metallen durch Anregung von Oberflächenplasma-schwingungen.” Z. Phys., 241: 313-324). In the Kretschmann configuration, a prism is used as a coupler between incident photons and surface plasmons on a surface of a thin metal film evaporated onto the prism. Since the refractive index of a prism is usually higher than the refractive index of its ambient environment (air or water), there is a critic incident angle θc for the light reflected inside the prism. Under the conditions when θ≧θc, total light reflection occurs inside the prism. For p-polarized light, the incident photons can excite surface plasmons on surface of a metal film. The incident angle for surface plasmon resonance is called resonance angle (θSPR). Since there is energy transfer from photons to surface plasmons during resonance, the reflectivity of incident light could change from 1 to 0 at θSPR. A graph of the relationship between reflectivity and incident angle is called an SPR spectrum.
Under some conditions, the shift of the resonance angle ΔθSPR is proportional to (ns−na)l, where ns and l are sample refractive index and thickness, na is the ambient refractive index. From the linear relationship, the amount of protein adsorbed on a gold film can be detected at as low as 0.01 ng/mm2, and the affinity of ligand-receptor interaction can be detected. After Nylander (Nylander, C., Liedberg, B. & Lind, T. (1982/83), “Gas detection by means of surface plasmon resonance” Sensors and Actuators, 3: 79-88) published the first paper about SPR biosensing in 1983, a project was initiated at Pharmacia of Sweden (Liedberg, B., C. Nylander, et al. (1995). “Biosensing with surface plasmon resonance—how it all started”, Biosensors and Bioelectronics 10(8): i-ix.) in 1984. In 1986 a separate company, Pharmacia Biosensor, was formed for the development of the new biosensor technology. Today the successful Pharmacia Biosensor Company is called Biacore (http://www.biacore.com) and it makes many kinds of commercial SPR biosensors. For biologists, these Biacore SPR biosensors are very useful, but also very expensive. The price of the latest model Biacore 3000 is presently about three hundred thousand dollars and the price of a disposable sensing chip is about one hundred and twenty dollars. A fully used Biacore SPR biosensor can consume thousands of the sensing chips per year.
U.S. Pat. Nos. 6,493,097 and 6,714,303 to Ivarsson et al. teach an apparatus and method of examining thin layer structures on a sensor surface by imaging light reflected by the surface during SPR microscopy. The apparatus uses a light source which illuminate collimator optics to produce a parallel light beam. The light beam passes an interference filter as a monochromatic beam and impinges on two flat scanner mirrors before the light beam is deflected into a prism or grating to the sensor surface. An optical system then produces an image of the sensor surface at a detector. The optical system adds cost and complexity to the apparatus.
While the related art teach surface plasmon resonance biosensors, there still exists a need for an inexpensive and portable surface plasmon resonance biosensor.